DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/18/2026 has been entered.
Withdrawn Rejections
The rejection of claims 31-32 under 112(b) are withdrawn in response to the amendments.
The rejections under 103 are withdrawn in response to the amendments. However, new grounds of rejection are set forth below.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/EP2020/076218, filed 09/21/2020, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/903,172, filed 09/20/2019.
Status of the Claims
Claims 1-8, 18-20, 22-23 and 29-34 are pending; claims 1-2, 8, 19, 22-23, 29 and 31 are amended; claims 9-17, 21 and 24-28 are cancelled; claims 19-20, 22-23 and 29 are withdrawn. Claims 1-8, 18 and 30-34 are examined below.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites “wherein the substrate comprises a substance capable of lowering the diffusibility of the product”.
However, it is not clear how the substrate can comprise a substance capable of lowering the diffusibility of the product because the substrate is converted into the product. Given that in order to produce the product the substrate needs to be converted into the product (“The substrate is converted into a product via a reaction with the conjugate at the respective test immobilization areas” specification page 14 lines 17-18), it is unclear how the substrate would lower the diffusibility of the product, or comprise a substance capable of lowering the diffusibility of the product. Because of this, a person having ordinary skill in the art would not be able to recognize the metes and bounds of the claim.
New Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3, 5-8, 18 and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Ifuku and Murai (US 20110014633 A1) ("Ifuku") (Cite No. 1 of IDS files 3/17/2022) in view of Rubin et al. (WO 0127626 A2) (“Rubin”)-Cite No. N of PTO 892 10/20/2025.
Regarding claim 1, Ifuku suggests an immunoassay analyzer for detecting at least one analyte in a liquid sample (“In the analysis system shown in FIG. 1, the antigen 3 is an analyte, an antigen-antibody reaction (sandwich method) is utilized as the selective interaction” paragraph 74, “As a sample containing the analyte, for example, blood (whole blood, plasma, serum), lymph, saliva, urine,…” paragraph 81) the immunoassay analyzer comprising: a transport matrix comprising a microporous membrane strip for transporting the liquid sample to at least one immobilization area along the transport matrix (“an analysis method comprising the steps of: (a) reacting a substance to be analyzed…(b) electrically analyzing the insoluble substance…wherein at least one of steps (a) and (b) is carried out under flow conditions” Abstract, “These flows may be used in various channels of a microfabricated flow, lateral flow, capillary flow, or flow-through, or a membrane strip for immunochromatography or the like” paragraph 116); at least one first capture reagent immobilized in the at least one immobilization area, the first capture reagent capable of binding with and thereby capturing the at least one analyte (“As still another preferred embodiment of the sensing part, a porous carrier such as a nitrocellulose membrane used in immunochromatography, a polymer as described in WO 2006/038456, or an insoluble carrier…may be used, to increase the surface area of the sensing part” para. 107, “The selective interaction reaction between an analyte and its specific partner is carried out at the place on which the specific partner is immobilized. The place where the specific partner is immobilized is not particularly limited, so long as the selective interaction is carried out, and then an electric measurement can be carried out. The surface of the sensing part is preferable” paragraph 110); and at least one amperometric or potentiometric sensor element comprising at least one first working electrode and at least one reference electrode (“Further, as the electric analysis method, an amperometric analysis using an electrode part having a working electrode 1, a counter electrode, and a reference electrode is used” paragraph 76) , wherein the first working electrode is configured to contact with the at least one immobilization area (paragraphs 107, 110, “The electric analysis method used in the present invention is not particularly limited, so long as an insoluble substance deposited on the surface of a sensing part is electrically analyzed” para. 97, “It is preferable that the reaction part "under flow conditions" is the insolubilization reaction part in which step (a) or step (a2) is carried out, and/or the sensing part in which step (b) is carried out” para. 114, para. 116) and the reference electrode is configured to contact with a portion of the transport matrix other than the at least one immobilization area (“An electrode part having a pattern as shown in FIG. 2 was constructed…. A gold thin film having a thickness of 50 mn was formed on an insulating substrate 11 made of polyethylene terephthalate (PET), and a silver/silver chloride ink (manufactured by BAS Inc.) was applied on a part of the gold thin film to construct a reference electrode 16…the electrode part having a working electrode 14, a counter electrode 15, and the reference electrode 16… The working electrode contained in the electrode part functions as a sensing part” paragraph 121, see Fig. 2). Note that Ifuku further suggests that each immobilization area is an area of the microporous membrane strip in which the at least one analyte will be immobilized when teaching that “lateral flow, capillary flow, or flow-through, or a membrane strip for immunochromatography or the like”, can be used for a transport matrix (paragraph 116); and also teaching that a “a porous carrier such as a nitrocellulose membrane used in immunochromatography…may be used” as part of the “sensing part”, which “can significantly increase the surface area of the sensing part, and as a result, the detection sensitivity can be improved” (paragraph 107). Given that Ifuku teaches that “[t]he place where the specific partner is immobilized is not particularly limited, so long as the selective interaction is carried out, and then an electric measurement can be carried out. The surface of the sensing part is preferable” (paragraph 110), this reads on the immobilization area being an area of the transport matrix comprising a microporous membrane strip because Ifuku teaches that the immobilization area may comprise a membrane; and also teaches that the transport matrix may be a membrane. Furthermore, Ifuku teaches that immunochromatography and current detection amperometric assay techniques are known (“For example, patent literature 1 discloses a combination of immunochromatography and a current-detection type amperometric assay” para. 3, “Although these prior art techniques are known” para. 11).
However, although suggested by Ifuku, Ifuku fails to explicitly teach that “each immobilization area is an area of the microporous membrane strip in which the at least one analyte will be immobilized”.
Rubin teaches “means and systems for carrying out immunoassays” (Title). Rubin further teaches “[a] system and corresponding method for carrying out an amperometric immunoassay of a target antigen in which a solid phase support is provided, having an oxidised cellulose paper on which is immobilised an antibody that specifically binds to target antigen and at least one enzyme. An electrode is juxtaposed with the paper, which is in communication with a reaction
chamber having suitable receiving means for providing thereto a test fluid having said target antigen and the chemicals required for the particular immunoassay reaction and a redox reaction occurring in response thereto to be carried out” (Abstract). Rubin further suggests that the microporous membrane strip in which the at least one analyte will be immobilized “is easily prepared… simple, of safe operation and inexpensive.” (page 5 paras. 3 and 8).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Ifuku to rely on the transport matrix comprising a microporous membrane strip for transporting the liquid sample to at least one immobilization areas along the transport matrix, each immobilization area being an area of the microporous membrane strip in which the at least one analyte will be immobilized taught by Rubin because Rubin suggests that this is safe to operate, simple and inexpensive for carrying out immunoassays and Ifuku is concerned with immunoassay analyzers. One would have been further motivated to make such a modification because Ifuku suggests that using a microporous membrane strip can significantly increase the surface area of the sensing part, and as a result, the detection sensitivity can be improved. A person having ordinary skill in the art would have had a reasonable expectation of success given that Ifuku teaches that the immobilization area is not particularly limited and suggests that the immobilization area may be an area of the transport matrix. Furthermore, Ifuku teaches that immunochromatography assays are known and both Ifuku and Rubin are concerned with amperometric immunoassays. Regarding claim 3, Ifuku in view of Rubin teach the immunoassay analyzer of claim 1 as discussed above.
Ifuku further teaches comprising a read-out circuit configured to determine a change in an electric current flowing through the first working electrode and the reference electrode (“Each electrochemical measurement was carried out, as shown in FIG. 8. More particularly, the connectors 40 to the working, reference, and counter electrodes were connected to an electrochemical analyzer 41 (model 832A; manufactured by ALS). The electric potential was varied between -0.15 V and 0.6 V with respect to the reference electrode, while passing the substrate solution containing silver ion or the pAPP substrate solution through the flow channel, to measure the electrochemical response by cyclic voltammetry (CV)” paragraph 129).
Regarding claim 5, Ifuku in view of Rubin teach the immunoassay analyzer of claim 1 as discussed above.
Ifuku further teaches wherein the reference electrode comprises gold (paragraph 121).
Regarding claims 6 and 33, Ifuku in view of Rubin teach the immunoassay analyzer of claim 1 as discussed above.
Ifuku further teaches further comprising a conjugate, the conjugate comprising a binding molecule specific to the at least one analyte, wherein the binding molecule is an antibody and wherein the conjugate further comprises an enzyme (“[i]n the analysis system shown in FIG. 1, an antibody 2 specific to the analyte (antigen) is immobilized on the working electrode 1 which constitutes an amperometric electrode part, and the working electrode functions as a sensing part. When a sample containing the analyte (antigen 3) and the ALP-labeled antibody 4 are supplied, along the flow direction represented by arrow A, from the upstream of the sensing part to the analysis system, a complex of immobilized antibody/antigen/ALP-labeled antibody is formed on the sensing part” paragraph 77, see Fig. 1, “an antibody which is specific to the antigen and is labeled with an enzyme such as alkaline phosphatase (ALP)” paragraph 74).
Regarding claims 7 and 34, Ifuku in view of Rubin teach the immunoassay analyzer of claim 1 as discussed above.
Ifuku further teaches a substrate convertible into a product via a reaction with the conjugate, wherein the substrate is convertible into a product via an enzymatic reaction with the conjugate (“[a]fter the formation of the complex, or simultaneously with the formation, p-aminophenylphosphate (pAPP), a substrate for the labeling enzyme ALP, is supplied from the upstream of the sensing part to the analysis system” paragraph 77, “an enzyme substrate or its reaction product” paragraph 84).
Regarding claim 8, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the substance capable of lowering the diffusibility of the product is interpreted to be comprised in the reaction solution. Ifuku in view of Rubin teach the immunoassay analyzer of claim 7 as discussed above.
Ifuku in view of Rubin further suggest wherein the substrate comprises a substance capable of lowering the diffusibility of the product (“The dried substrate was immersed in
a 0.1 mol/L Tris buffer (pH 8.0) containing 1 % casein (manufactured by Waka Pure Chemical Industries, Ltd.) and 0.15 mol/L NaCl for 30 minutes while shaking” para. 122). Note that the specification page 7 lines 16-17 discloses that “the substrate preferably comprises a substance capable of lowering the diffusibility of the product, the substance, for example, comprising saccharides or gels”. Therefore, the casein and NaCl comprised in the substrate reaction medium would inherently lower the diffusibility of the product because these create more viscosity and density in the solution, thereby lowering diffusibility.
Regarding claim 18, Ifuku in view of Rubin teach the immunoassay analyzer of claim 1 as discussed above.
Ifuku further suggests an immunoassay kit, comprising the immunoassay analyzer of claim 1, a conjugate comprising a binding molecule specific to the analyte, and a substrate convertible into a product via a reaction with the conjugate (paragraph 77, “kit for measuring a substance to be analyzed” claims 16-17).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Ifuku in view of Rubin as applied to claim 1 above, and further in view of Tatsushi et al. (WO 2006038456 A1)-Cite No. O of PTO 892 10/20/2025 (“Tatsushi”), Anfossi et al. Analytical and Bioanalytical Chemistry (2019) 411:1905–1913 https://doi.org/10.1007/s00216-018-1451-6 (“Anfossi”) and Pakchin et al. Trends in Analytical Chemistry 92 (2017) 32e41 http://dx.doi.org/10.1016/j.trac.2017.04.010 (“Pakchin”).
Regarding claim 2, Ifuku in view of Rubin teach the immunoassay analyzer of claim 1, wherein the first capture reagent is immobilized in a first immobilization area and capable of binding with and thereby capturing a first analyte in the liquid sample as discussed above.
Rubin further teaches that “various electrodes can be used” (page 11 para. 5).
Ifuku in view of Rubin fail to teach the immunoassay analyzer further comprising: a second capture reagent immobilized in a second immobilization area, the second capture reagent capable of binding with and thereby capturing a second analyte in the liquid sample, the second immobilization area being downstream of the first immobilization area, wherein the sensor element further comprises a second working electrode configured to contact with the second immobilization area.
Tatsushi teaches a “solid support with biomaterial fixed thereon” (Title). Tatsushi further teaches a that “[t]he solid phase carrier serves as a substrate for forming the biological material structure” (page 62 para. 5), and that the substrates may “include chips (substrates) on which a large number of biological substances can be arranged…porous membranes…and the like” (page 62 last paragraph and page 63 para. 1). Tatsushi further suggests a transport matrix (“substrate having a flow path formed thereon, and the biological material structure held on the substrate” page 9 last paragraph). Tatsushi further teaches that the biomaterial fixed thereon may be an antibody for capturing and detecting an antigen analyte in a liquid sample (“such an assembly method can also deliver a specimen or the like to the biological substance-immobilized carrier or array of the present invention under flow conditions. At this time, it is preferable that at least the specimen is a fluid, and more preferably, other reagents are fluid. First, a cell (flow cell) containing a biological substance-immobilized carrier in which an antibody (primary antibody) against an antigen as an analyte is immobilized together with a support and a compound for supporting immobilization is prepared” page 133 last paragraph, see Figure 6 and claims). Tatsushi further suggests a second capture reagent immobilized in a second immobilization area, the second capture reagent capable of binding with and thereby capturing a second analyte in the liquid sample (“The biological material-immobilized carrier of the present invention is a solid phase carrier on which a biological material is immobilized, and has a predetermined matrix on the surface of the solid phase carrier…the array of the present invention is produced by arranging at least two or more of the predetermined matrix forces in separate regions on the solid phase carrier” page 108 paragraphs 2-3, “two or more types of analytes are assayed …Such a method is very useful, for example, as “panel inspection” or “profile inspection”. A panel test means that a more detailed examination of a disease or symptom is performed by combining multiple test markers. For example, when diagnosing cancer, it is difficult to identify which cancer is just because the value of one tumor marker is high, but by examining multiple tumor markers, The type and location of the tumor can be narrowed down” page 134 para. 2). Tatsushi further teaches that “specific examples of biosensors to which the biological substance-immobilized carrier of the present invention can be applied include…electrode method…sensors using electrochemical methods” (page 132 para. 3).
Anfossi teaches “multiplex lateral flow immunoassay (xLFIA)” (Abstract). Anfossi further teaches that “[i]n order to answer to the pressing demand for multiplexing LFA, several approaches have been exploited… (i) combining several strips (each targeting an individual analyte) in a single cassette, (ii) spatially separating the detection sites on one strip… The first approach has major limitations, such as being expensive (the material expenditure for the fabrication of the device increases proportionally with the number of analytes being detected) and requiring large sample volumes. Therefore, the second strategy has been exploited more frequently [4–6]. In this case, the LFA strip comprises several successive zones each containing a different capturing reagent with specificity towards a different target… This approach decreases expenditure on assay materials and sample volumes required” (page 1905 col. 2 para. 2 and page 1906 col. 1 para. 1). See figure 1 o Anfossi showing the second immobilization area being downstream of the first immobilization area.
Pakchin teaches “simultaneous electrochemical multi-analyte sensing platforms” (Title). Pakchin further teaches that “[s]imultaneous sensing of multiple biomarkers by electrochemical techniques can be achieved through either multi-label or multi-electrode approaches” (Abstract). Pakchin further suggests that wherein the sensor element further comprises a second working electrode configured to contact with the second immobilization area, i.e. the multi-electrode approach enables robust, user friendly, sensitive and accurate measurements (“Multi-electrode approach in simultaneous biomarker detection is one of two main strategies. The main advantages of these platforms in comparison with multi-label platforms include their robustness, user friendly, sensitivity and accuracy [71]. The multi-electrode platforms employ two or more sensing areas that may vary in construction. The sensing area may place in one operating region or lay in different individual electrodes” page 36 col. 2 para. 6 and page 37 col. 1 para. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Ifuku in view of Rubin to rely on the second capture reagent immobilized in a second immobilization area, the second capture reagent capable of binding with and thereby capturing a second analyte in the liquid sample suggested by Tatsushi because Tatsushi suggests that this enables a "panel inspection" or "profile inspection" that can provide a more detailed analysis in diagnosing disease; for example, in diagnosing cancer, for narrowing down the type and location of a tumor. A person having ordinary skill in the art would have had a reasonable expectation of success given that Ifuku references Tatsushi as teaching a suitable sensing area for the immunoassay analyzer (Ifuku para. 107). Furthermore, both Ifuku and Tatsushi teach immunoassay analyzers for detecting at least one analyte in a liquid sample comprising a transport matrix, at least one first capture reagent immobilized in the immobilization area, and an electrode for carrying out the measurement.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Ifuku in view of Rubin and Tatsushi to rely on the second immobilization area being downstream of the first immobilization area taught by Anfossi because Anfossi teaches that this approach decreases expenditure on assay materials and sample volumes required. A person having ordinary skill in the art would have had a reasonable expectation of success because both Ifuku and Anfossi are drawn to an immunoassay analyzer for detecting at least one analyte in a liquid sample.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Ifuku in view of Rubin, Tatsushi and Anfossi to rely on the second electrode configured to contact with the second immobilization area taught by Pakchin because Pakchin teaches that this enables robust, user friendly, sensitive and accurate measurements. A person having ordinary skill in the art would have had a reasonable expectation of success because Pakchin teaches that using a second electrode is one of two possible ways to detect a second analyte using electrochemical multi-analyte sensing platforms and both Ifuku and Pakchin are drawn to electrochemical detection of at least one analyte.
Claims 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Ifuku in view of Rubin, Tatsushi, Anfossi and Pakchin as applied to claim 2 above, and further in view of Prasad (WO 2018075824 A1)-Cite No. N of PTO892 6/3/2025 (“Prasad”).
Regarding claims 31-32, Ifuku in view of Rubin, Tatsushi, Anfossi and Pakchin teach the immunoassay analyzer of claim 2 as discussed above.
Ifuku further teaches further comprising: a read-out circuit configured to determine an electric potential difference between the first working electrode and the reference electrode or a change in an electric current flowing through the first working electrode and the reference electrode (para. 129).
Ifuku in view of Rubin, Tatsushi, Anfossi and Pakchin fail to teach wherein the read-out circuit is configured to further determine an electric potential difference between the second working electrode and the reference electrode or a change in an electric current flowing through the second working electrode and the reference electrode, wherein the read-out circuit is configured to determine a respective amount of the at least one analyte based on the respective change in the electric current.
Prasad teaches an immunoassay analyzer for detecting at least one analyte in a liquid sample (“devices, apparatus, systems, methods and kits for performing immunoassay tests on a sample” Abstract, “highly specific biomarkers can be detected rapidly at ultralow concentrations from very low fluid sample volumes from a user” paragraph 6), the immunoassay analyzer comprising: a transport matrix for transporting the liquid sample to at least one immobilization area along the transport matrix (“Referring to FIG. 1, the sensing device 100 may comprise a substrate 110” paragraph 89, “the substrate may comprise test strips for aiding lateral transport of a sample fluid to electrodes on the sensing device. Non-limiting examples of test strips may include porous paper, or a membrane polymer such as nitrocellulose, polyvinylidene fluoride, nylon, Fusion 5™, or polyether sulfone” paragraph 90); at least one first capture reagent (“[t]he capture reagents may be disposed” paragraph 87), the first capture reagent capable of binding with and thereby capturing the at least one analyte (“The plurality of capture reagents are configured to selectively bind to one or more target analytes in a fluid sample” paragraph 106); and at least one amperometric or potentiometric sensor element comprising at least one first working electrode and at least one reference electrode (“a first sensing device may comprise a working electrode, a counter electrode and a reference electrode located in proximity to each other in a first region of the substrate” paragraph 30, “[t]he output from each sensing device may be independently measured and transduced (e.g., amperometric or impedometric) to provide a combinatorial/multiplexed result relating to the end physiological state being predicted” paragraph 155), wherein the first working electrode is configured to contact with the at least one immobilization area (“A working electrode in each sensing device can be independently functionalized for specific detection of a target analyte which may be a biomarker” paragraph 155) and the reference electrode is configured to contact with a portion of the transport matrix other than the at least one immobilization area (“[t]he common reference electrode can provide a stable and known electrode potential to the electrochemical cell comprising of the first and second sensing devices” paragraph 159, See Fig. 5, “The RE [reference electrode] 130 and CE 140 may each comprise a conducting electrode stack, and need not comprise sensing elements on their surfaces. For example, the RE 130 and CE 140 need not include molecules that are used for functionalizing the sensing element on the WE 120.” Paragraph 93). Prasad further teaches a second capture reagent, the second capture reagent capable of binding with and thereby capturing a second analyte in the liquid sample, , wherein the sensor element further comprises a second working electrode configured to contact with the second immobilization area (“As shown in FIG. 5, a first capture reagent 124-1 may be attached to the first semiconducting nanostructures 122-1 on the first electrode 120-1, and configured to selectively bind to a first target analyte 128-1. A second capture reagent 124-2 may be attached to the second semiconducting nanostructures 122-2 on the second electrode 120-2, and configured to selectively bind to a second target analyte 128” paragraph 169). Prasad further teaches that “[a] test strip may comprise sensing array that are functionalized to detect analytes of interest. Test strips comprising different types of sensing arrays can be provided… The diagnostic reader device 1420 can be configured for use with the test strip… The reader device may comprise, for example the multiplexer 150, sensing circuitry 160, and/or computing device 170 shown in FIG. 5. The reader device can be configured to perform electroanalytical diagnostics on the test strip substantially in real-time” (paragraphs 218-219). Prasad further teaches further comprising: a read-out circuit configured to determine an electric potential difference between the first working electrode and the reference electrode or a change in an electric current flowing through the first working electrode and the reference electrode, wherein the read-out circuit is configured to further determine an electric potential difference between the second working electrode and the reference electrode or a change in an electric current flowing through the second working electrode and the reference electrode (paragraphs 155, 175-176, “The open circuit (OC) potential at both the first and second sensing devices is measured to establish that the same electric potential exists on both sensing devices of the array. This corresponds to the potential experienced at the working electrode relative to the reference electrode prior to occurrence of an electrochemical reaction, and is estimated at 0.02 V, i.e. 25.0 ±1.8 mV in the first sensing device and 24.6 ±1.6 mV in the second sensing device” paragraph 200). Prasad further teaches wherein the read-out circuit is configured to determine a respective amount of the at least one analyte based on the respective change in the electric current (paragraph 14). Prasad further suggests that this enables “simultaneous and multiplexed detection of multiple target analytes” (paragraph 153) which “can provide significant advantages for point of care diagnostics…[such as] performance of both negative and positive controls in the same sample….[and] improve[ment of] the specificity and sensitivity with which certain diseases and physiological conditions can be detected and diagnosed” (paragraph 154).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Ifuku in view of Rubin, Tatsushi, Anfossi and Pakchin to rely on a read-out circuit being configured to further determine an electric potential difference between the second working electrode and the reference electrode or a change in an electric current flowing through the second working electrode and the reference electrode, wherein the read-out circuit is configured to determine a respective amount of the at least one analyte based on the respective change in the electric current taught by Prasad because Prasad suggests that this provides significant advantages for point of care diagnostics such as performance of both negative and positive controls in the same sample and improved specificity and sensitivity as well as electroanalytical diagnostics on the test strip substantially in real-time. A person having ordinary skill in the art would have had a reasonable expectation of success given that both Ifuku and Prasad teach immunoassay analyzers for detecting at least one analyte in a liquid sample comprising a transport matrix, at least one first capture reagent immobilized in the immobilization area, and working and reference electrodes for carrying out the amperometric or potentiometric measurement.
Claims 4 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Ifuku Rubin as applied to claim 1 above, and further in view of Prasad.
Regarding claim 4, Ifuku in view of Rubin teach the immunoassay analyzer of claim 1 as discussed above.
Ifuku in view of Rubin fail to teach wherein the first or second working electrode is an ion-selective electrode (ISE).
Prasad further teaches wherein the first or second working electrode is an ion-selective electrode (ISE) (“The sensing platform may be configured to perform immunoassays as described elsewhere herein” paragraph 214, “An example of a POC application using the sensing platform 1400 is next described. A disposable sensing array comprising of IL/ZnO hybrid liquid/solid semiconducting electrode, is functionalized with antibodies that are receptors for the panel of protein biomarkers to be tested” paragraph 231, “the sensing platform 1400 can be used in aptasensing for K + detection. Aptamer oligonucleotides that contain single or multiple guanine-rich segments are known to form specific four-stranded helical conformations in solution with an extraordinary selectivity for potassium… from human blood… towards real-time detection and monitoring levels of… potassium… from finger-pricked capillary blood” paragraphs 232-233).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Ifuku in view of Rubin to rely on the first working electrode being an ion-selective electrode taught by Prasad because Prasad teaches that this enables detection of blood potassium levels in real time and Ifuku is concerned with detecting at least one analyte. A person having ordinary skill in the art would have had a reasonable expectation of success given that both Ifuku and Prasad teach immunoassay analyzers for detecting at least one analyte in a liquid sample comprising a transport matrix, at least one first capture reagent immobilized in the immobilization area, and working and reference electrodes for carrying out the amperometric or potentiometric measurement.
Regarding claim 30, Ifuku in view of Rubin Prasad teach the immunoassay analyzer of claim 4 as discussed above.
Ifuku further suggests wherein the first working electrode is an oxidation-reduction potential (ORP) electrode (“The present invention relates to an analysis method utilizing...an insolubilization reaction (preferably an oxidation-reduction reaction)… and
characterized in that at least one of the insolubilization reaction and the electric analysis is carried out under flow conditions” paragraph 70, “as the electric analysis method, an amperometric analysis using an electrode part having a working electrode 1, a counter electrode, and a reference electrode is used” paragraph 76).
Response to Arguments
Applicant's arguments filed 2/18/2026 have been fully considered but they are not persuasive.
Regarding the 103 rejections,
Applicant argues that “Although the Office Action cites paragraph [0107] of Ifuku, which refers to the use of a porous material to increase surface area, Ifuku teaches that this porous material forms part of the conductive sensing part (a "carrier" is used to "increase the surface area of the sensing part") and thus still functions as a working electrode, rather than as a transport medium for fluid flow. That is, the carrier of Ifuku defines (at least in part) the "surface area" of the electrode and is thus simply a part of the electrode” (page 8 para. 2).
However, Ifuku suggests that the porous carrier is part of the transport matrix when teaching that the fluid flow may be generated by capillary action through a membrane strip for immunochromatography (para. 116) and also teaching that the carrier may be a membrane strip for immunochromatography (para. 107). Therefore, although the carrier increases the surface area of the sensing part, it would also be capable of transporting the fluid. Nevertheless, new grounds of rejection are set forth above (see rejection above) in view of Rubin who clearly teaches that the microporous membrane strip is separate and in contact with the electrode (“electrode is juxtaposed with the paper” Abstract).
Applicant further argues that “The Advisory Action argues that the claim does not "limit the transport matrix to be a single structure" and therefore that "the teachings of Ifuku regarding placing the working electrode and reference electrode in a different portions [sic] of the microchannel inherently provides the required placement of the reference electrode recited by claim 1."” (page 8 para. 4).
However, the cited portion of the Advisory Action attempted to respond to the argument from 2/19/2025 regarding that the flow channel of Ifuku was being interpreted as the transport matrix (see page 8 last paragraph of the arguments from 2/19/2025). However, as mentioned above, Ifuku suggests that the transport matrix is a membrane for immunochromatography. Nevertheless, new grounds of rejection are set forth above in view of Rubin (see rejection above).
Applicant further argues that “Thus, in the configuration of paragraph [0107] of Ikuku, the capture reagent is disposed on the three-dimensional structure, rather than within the transport matrix itself. Ifuku discusses (for instance, at paragraphs [0108], [0110], and [0114] to [0119]) that there is both immobilization of a partner and "flow conditions", and discusses a nitrocellulose membrane as being part of the sensor/electrode (rather than a separate or separable part)” (page 10 paras. 3-4).
However, as stated above, the structure of paragraph 107 of Ifuku is interpreted as part of the transport matrix and not part of the electrode. Indeed, the fact that Ifuku defines the distinction between sensor/electrode and membrane suggests that the membrane in not part of the electrode. Nevertheless, new grounds of rejection are set forth above (see rejection above) in view of Rubin who clearly teaches a separate microporous membrane juxtaposed to the electrode.
Applicant further argues that “As shown in Figures 4-7 of Ifuku (in particular, Figure 7, reproduced below), Ifuku relies on a flow channel 25 to establish flow conditions” (page 11 para. 1).
However, Ifuku also relies on capillary flow to establish flow conditions (para. 116 of Ifuku). See rejection above.
Applicant further argues that “Ifuku's working electrode and reference electrode are configured to contact the same liquid sample volume. Accordingly, a person of ordinary skill in the art following Ifuku would place both electrodes in contact with the same area of the transport matrix” (page 12 para. 3).
However, given that Ifuku teaches that the measurement happens “under flow conditions” (Abstract), this would inherently prevent the working electrode and reference electrode to contact the same liquid volume.
Applicant further argues that “all of the pending claims are in condition for allowance… rejoinder and allowance of the withdrawn claims is respectfully requested” (page 13 paras. 3-4).
However, no claim is allowed.
Conclusion
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/Fernando Ivich/Examiner, Art Unit 1678
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677